A Common R219K Variant of ATP-Binding Cassette Transporter A1 Gene Alters Atherometabolic Traits in Pregnant Women With Gestational Diabetes Mellitus

Fangmei Tang; Linbo Guan; Xinghui Liu; Ping Fan; Mi Zhou; Yujie Wu; Rui Liu; Yu Liu; Sixu Liu; Dehua Li; Huai Bai

doi:10.3389/fendo.2021.782453

A Common R219K Variant of ATP-Binding Cassette Transporter A1 Gene Alters Atherometabolic Traits in Pregnant Women With Gestational Diabetes Mellitus

Front Endocrinol (Lausanne). 2021 Dec 17:12:782453. doi: 10.3389/fendo.2021.782453. eCollection 2021.

Authors

Fangmei Tang^{1

2}, Linbo Guan¹, Xinghui Liu³, Ping Fan¹, Mi Zhou³, Yujie Wu³, Rui Liu⁴, Yu Liu⁵, Sixu Liu^{1

2}, Dehua Li^{1

2}, Huai Bai¹

Affiliations

¹ Laboratory of Genetic Disease and Perinatal Medicine and Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
² West China School of Nursing, Sichuan University, Chengdu, China.
³ Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
⁴ Division of Peptides Related With Human Disease, West China Hospital, Sichuan University, Chengdu, China.
⁵ Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.

Abstract

Background: ATP-binding cassette transporter A1 (ABCA1) has important roles in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport, and is implicated in lipid-related disorders. Genetic variants are involved in the pathogenesis of gestational diabetes mellitus (GDM). The objective of this study was to investigate the association of rs2230806 (R219K), a single nucleotide polymorphism (SNP) in the lipid-related gene, with the risk of GDM and related traits.

Methods: The SNP, rs2230806, was genotyped, and clinical and metabolic parameters were determined in 660 GDM patients and 1,097 control subjects. Genetic associations with related traits were also analyzed.

Results: The genotype distributions were similar in GDM patients and normal controls. However, significant differences in the variables examined in the study subjects were noted across the three genotypes. The genotype at the rs2230806 polymorphism was significantly associated with HDL-cholesterol (HDL-C) levels and atherogenic index (AI) values in GDM patients and total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels in control subjects. Subgroup analysis showed that the polymorphism was associated with diastolic blood pressure, in addition to HDL-C levels and AI, in overweight/obese GDM patients, while it was associated with TC levels, AI, pre-pregnancy body mass index (BMI), and BMI at delivery in non-obese GDM patients. In addition, this polymorphism was associated with TC, LDL-C, and apoB levels in overweight/obese control subjects.

Conclusions: The rs2230806 polymorphism in the ABCA1 gene was associated with variations in atherometabolic traits in GDM patients, with characteristics of BMI dependency, but not with GDM. Our findings highlight a link between related phenotypes in women with GDM and genetic factors.

Keywords: ABCA1 gene; atherometabolic traits; gestational diabetes mellitus; obesity; single nucleotide polymorphism (SNP).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter 1 / genetics*
Atherosclerosis / blood
Atherosclerosis / epidemiology
Atherosclerosis / genetics
China / epidemiology
Cholesterol, HDL / blood
Cholesterol, LDL / blood
Diabetes, Gestational / blood*
Diabetes, Gestational / epidemiology
Diabetes, Gestational / genetics*
Female
Genetic Variation / genetics*
Humans
Overweight / blood
Overweight / epidemiology
Overweight / genetics
Polymorphism, Single Nucleotide / genetics*
Pregnancy
Pregnant Women

Substances

ABCA1 protein, human
ATP Binding Cassette Transporter 1
Cholesterol, HDL
Cholesterol, LDL